Today Otsuka presented results from a pre-specified interim analysis from its phase 3 VISIONARY study. This late-stage trial was testing the use of sibeprenlimab for the treatment of adult patients with immunoglobulin A nephropathy (IgAN). This disease is caused by the building of abnormal immunoglobulin A antibodies that accumulate in the kidneys, specifically in the glomeruli of the organ itself. In turn, this aggressive buildup of antibodies causes inflammation and damage, leading to a host of symptoms for patients. The interim analysis performed revealed that patients treated with this drug were able to achieve a reduction in proteinuria of 51.2% at nine months when compared to that of placebo. This pre-specified interim analysis efficacy endpoint was met with a statistically significant p-value of p<0.0001.
This endpoint was measured by a 24-hour urine protein-to-creatinine (uPCR) ratio at nine months compared to that of placebo. The point of this measure is to see the amount of protein and creatinine developed in a 24-hour period. A higher uPCR correlates with kidney damage, and thus a vast amount of deposits are generated. Not only was this particular efficacy achieved, but it was done so with sibeprenlimab being similar to that of placebo in terms of treatment-emergent adverse events [TEAs]. The premise is that proteinuria reduction may delay a person from progressing to kidney failure. With that being said, this endpoint was used as a surrogate biomarker so that the company could file its Biologics Licensing Application [BLA] of this drug for the treatment of patients with IgA to the FDA.
The FDA not only accepted its BLA of sibeprenlimab last month but also granted it a Priority Review Designation with a Prescription Drug User Fee Act (PDUFA) target action date of November 28th of 2025. If the FDA agrees that the safety and efficacy data supports regulatory approval, then Otsuka is well in line to receive U.S. marketing authorization for it. The company just didn’t file the BLA on the basis of only the phase 3 VISIONARY study, where it met the pre-specified interim analysis; it also did so on the basis of a positive outcome from the phase 2 ENVISION trial. Of course, the evaluation of proteinuria is just a biomarker to show the reduction of kidney damage. The company is expected to continue the late-stage VISIONARY trial in a blinded manner to evaluate how the kidneys evolve over a 24-month period when patients are given this once-monthly subcutaneous injection of APRIL inhibitor. This particular efficacy endpoint is going to be measured using estimated glomerular filtration rate (eGFR), and the final outcome from such an evaluation is expected to happen in early 2026.
APRIL is a cytokine that is crucial to IgAN pathogenesis. In particular, this A Proliferation-Inducing Ligand (APRIL) is a member of the tumor necrosis factor (TNF) family that plays an important part in B-cell formation leading to immune complex formation. Sibeprenlimab is an APRIL inhibitor developed to bind to this cytokine, and the aim for it is to reduce the amount of IgA and Gd-IgA1 levels as a result of the immune complex formation that drives this disorder. Beyond the scope of the company potentially receiving U.S. marketing approval of sibeprenlimab for the treatment of patients with IgAN, it is possible that the company can apply this clinical candidate to other autoimmune disorders. Especially since many of them are also driven by B-cell immune response activity.
IgA nephropathy is a type of autoimmune disorder that is responsible for depositing a lot of antibodies into the kidney of a patient. Specifically, there is inflammation and damage of the kidneys because antibodies, known as immunoglobulin A (IgA), attack the small blood vessels of the kidney, which are glomeruli. The whole point of sibeprenlimab is to be a disease-modifying therapy that would work to reduce proteinuria in urine and prevent the patient from moving on towards something more deadly later on, such as kidney failure.